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Dr. Valerian E Kagan, PhD, DSc

Professor, Environmental and Occupational Health

Contact

Environmental and Occupational Health, 100 Technology Drive, BRIDG 328, Pittsburgh, PA 15219
R-znvy: xntna@cvgg.rqh
Primary Phone: 967-179-4924
Secondary Phone: 967-179-4255
Fax: 967-179-4816
Web site:


Personal Statement

Dr. Valerian E. Kagan is one of the world’s recognized leaders and one of the most prominent authorities in the field of Free Radical Biology and Medicine.  Internationally known for his profound interdisciplinary studies of oxidative stress, antioxidants, tissue and cell acute and chronic injury, he has founded a new field of research “Oxidative Lipidomics” and demonstrated its research power in investigations of cell death mechanisms. Free radicals, lipid peroxidation and oxidative stress have been long associated with tissue and cell damage through yet not well characterized specific mechanisms.  The incompleteness of this knowledge is a stumbling block in discovery, development and effective implementation of antioxidant preventive and therapeutic strategies.  The research performed by Dr. Kagan is a breakthrough in the field as it uncovers specific pathways through
which enzymes of oxidative metabolism participate in the production of specific oxygenated lipid molecules that act as signals triggering cell death program as well as mechanisms involved in clearance of damaged or dead cells. Understanding these key signaling pathways is of prime importance for obtaining new insights into mechanisms of radiation injury, inflammation, and immune responses.  Based on the discoveries of Dr. Kagan’s lab mechanism-based approaches to
creation of novel generations of preventive, protective and mitigating small molecule drugs have been developed that are being tested in a number of conditions.


Education

1967 -  MV Lomonosov Moscow State University, Russia, BS - Biochemistry, Biophysics
1978 -  MV Lomonosov Moscow State University, Russia, MS - Biochemistry, Biophysics
1972 -  MV Lomonosov Moscow State University, Russia, PhD- Biochemistry, Biophyscis
1981 - USSR Academy of Sciences, Russia, DSc - Biochemistry, Biophysics
1983 - State Prize of the USSR for Science (in the former USSR, the top 10-15 programs in Science were 
            annual awarded this prize.
2012 - Fellow, The American Association for the Advancement of Science


Teaching

Introduction to Research Methods I and II: Instructor
Biochemical Techniques in Molecular Toxicology: Instructor
Cancer Biology and Therapeutics (Graduate Pharmacology Course Series): Lecturer
Principles of Toxicology: Lecturer
Molecular Fundamentals: Lecturer
Molecular Biophysics 2: Biomolecular Interactions and Dynamics: Lecturer


Selected Publications

Tejero J, Kapralov AA, Baumgartner MP, Sparacin-Watkins CE, Anthonymutu TS, Vlasova II, Camachu CJ, Gladwin MT, Bayir,
H, Kagan VE.  Peroxidase activation of cytoglobin by anionic phospholipids: Mechanisms and consequences.  Biochim Biophys Acta. 2016 May;
1861(5):391-401.  PMID:2698591.

Banerjee K, Munshi S, Xu H, Frank DE, Chen HL, Chu CT, Yang J, Cho S, Kagan VE, Denton TT, Tyurina YY, Jiang JF, Gibson GE. Mild mitochondrial metabolic deficits by ɑ-ketoglutarate dehydrogenase inhibition cause prominent changes in intracellular autophagic signaling: Potential role in the pathobiology of Alzheimer’s disease.  Neurochem Int. 2016 Jun;96:32-45. PMID:26923918.

Huang Z, Epperly M, Watkins SC, Greenberger JS, Kagan VE, Bayir H.  Necrostatin-1 rescues mice from lethal irradiation. Biochim Biophys Acta. 2016 Apr; 1862(4):850-6. PMID: 26802452.

Vlasova II, Kapralov AA, Michael ZP, Burkert SC, Shurin MR, Star A, Shvedova AA, Kagan VE.  Enzymatic oxidative biodegradatin of nanoparticles: Mechanisms, significance and applications.  Toxicol
Appl Pharmacol. 2016 May; 15;299-58-69. PMID: 26768553.

Mao G, Qu F, St Croix CM, Tyurina YY, Planas-Iglesias J, Jiang J, Huang Z, Amoscato AA, Tyurina VA, Kapralov AA, Cheikhi A, Maguire J, Klein-Seetharaman J, Bayir H, Kagan VE.  Mitochondrial
Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals. ACS Chem Biol. 2016. Feb 19;11(2):530-40. Epub 2016 Jan 5. PMID: 26697918.

Zou C, Synan MJ, Li J, Xiong S, Manni ML, Liu Y, Chem BB, Zhao Y, Shiva S, Tyurina YY, Jiang J, Lee JS, Das S, Ray A, Ray P, Kagan VE, Mallampalli RK.  LPS impairs oxygen utilization in epithelia by triggering degradation of the mitochondrial enzyme Alcat1.  J Cell Sci. 2016 Jan
1;129(1):51-64. Epub 2015 Nov 24. PMID:26604221.

 

 

Shvedova AA, Kisin ER, Yanamala N, Farcas MT, Menas AL, Williams A, Fournier PM, Reynolds JS, Gutkin DW, Star A, Reiner RS, Halappanavar S, Kagan VE.  Gender differences in murine pulmonary responses elicited by cellulose nanocrystals.  Part Fibre Toxicol. 2016 Jun 8;13(1):28. PMID: 27278671.

Buland JR, Wasserloos KJ, Tyurin VA, Tyurina
YY, Amoscato AA, Mallampalli RK, Chen BB, Zhao J, Zhao Y, Ofori-Acquah S, Kagan VE, Pitt BR.  Biosynthesis of Oxidized Lipid Mediators via Lipoprotein Associated Phospholipase A2 Hydrolysis of
Extracellular Cardiolipin Induces Endothelial Toxicity. Am J Physiol Lung Cell Mol Physiol. 2016 Aug 1;311(2):L303-16. PMID: 27233995.

 

 

 

Maguire JJ, Tyurina YY, Mohammadyani D,
Kapralov AA, Anthonymuthu TS, Qu F, Amoscato AA, Sparvero LJ, Tyurin VA, Planas-Iglesias J, He RR, Klein-Seetharaman J, Bayir H, Kagan VE. Known unknowns of cardiolipin signaling: The best is yet to come. Biochim Biophys Acta. 2016 Aug 4 [Epub ahead of print] PMID: 27498292.

Fidan E, Lewis J, Kline AE, Garman RH, Alexander H, Cheng JP, Bondi CO, Clark R, Dezfulian C, Kochanek PM, Kagan VE, Bayır H. Repetitive mild traumatic brain injury in the developing brain: effects on long-term functional outcome and neuropathology. J Neurotrauma. 2016 Apr 1;33(7):641-51.  PMID: 26214116.

 Sparvero LJ, Amoscato AA, Fink AB, Anthonymuthu T, New LE, Kochanek PM, Watkins S, Kagan VE, Bayir H. Imaging Mass Spectrometry Reveals Loss of Polyunsaturated Cardiolipins in the Cortical Contusion, Hippocampus and Thalamus after Traumatic Brain Injury. J Neurochem.  2016 Nov 139(4):659-675. PMID:27591733.

Kagan VE, Jiang J, Huang Z, Tyurina YY, Desbourdes C, Cottet-Rousselle
C, Dar HH, Verma M, Tyurin VA, Kapralov AA, Cheikhi A, Mao G, Stolz D, St Croix CM, Watkins S, Shen Z, Li Y, Greenberg ML, Tokarska-Schlattner M, Boissan M, Lacombe ML, Epand RM, Chu CT, Mallampali RK, Bayir H, Schlattner U.  NDPK-D (NM23-H4)-mediated externalization of
cardiolipin enables elimination of depolarized mitochondria by mitophagy. Cell Death Differ. 2016 Jul 23;(7):1140-51. PMID: 26742431.

Ouyang Y, Bayer A, Chu T, Tyurin VA, Kagan VE, Morelli AE, Coyne CB, Sadovsky Y.  Isolation of human trophoblastic extraclllar vesicles and
characterization of their cargo and antiviral activity.  Placenta. 2016 Nov;47:86-95. PMID: 27780544.

Olonisakin TF, Li H, Xiong Z, Kochman EJ, Yu M, Qu Y, Hulver M, Kolls JK, St Croix C, Doi Y, Nguyen MH, Shanks RM, Mallampalli RK, Kagan VE, Ray A, Siverstein RL, Ray P, Lee JS. CD36 Provides Host Protection Against Klebsiella pneumoniae Intrapulmonary Infection by Enhancing Lipopolysaccharide Responsiveness and Macrophage Phagocytosis. J Infect Dis. 2016 Dec 15;214(12):1865-1875. PMID: 27683817.

Mahapatra G, Varughese A, Ji Q, Lee I, Liu J, Vaishnav A, Sinkler C, Kapralov AA, Moraes CT, Sanderson TH, Stemmier TL,
Grossman LI, Kagan VE, Brunzelle JS, Salomon AR, Edwards BF, Hüttemann M.Phosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney: IMPLICATIONS FOR AMP KINASE. J Biol Chem. 2017 Jan 6; 292(1):64-89. PMID: 27758862.

Tian H, Sparvero LJ, Amoscato AA, Bloom A, Bayir H, Kagan VE, Winograd N. Gas Cluster Ion Beam Time-of-Flight Secondary Ion Mass Spectrometry High-Resolution Imaging of Cardiolipin Speciation in the Brain: Identification of Molecular Losses after Traumatic Injury.  Anal
Chem.  2017 Apr 18;89(8):4611-4619. doi:
10.1021/acs.analchem. 7b00164. [Epub ahead of print] PMID: 28306235.

 Chiu CF, Saidi WA, Kagan, VE, Star A.  Defect-Induced Near-Infrared
Photoluminescence of Single-Walled Carbon Nanotubes Treated with
Polyunsaturated Fatty Acids. J Am Chem Soc. 2017 Mar 22. doi:
10.1021/jacs.7b00390.  [Epub ahead of print] PMID: 28288512.

Kagan VE, Bayir H, Tyurina YY, Bolevich SB, Maguire JJ, Fadeel B, Balasubramanian K.  Elimination of the unncesary: Intra-and
extracellular signaling by anionic phospholipids. Biochem Biop;hys Res Commun. 2017 Jan 15;(3):482-490.doi: 10.1016/.bbrc.2016.11.005 Epub 2017 Feb 3. Review. PMID: 28212735.

 Chakraborty K, Raundhal M, Chen BB, Morse C, Tyurina YY, Khare A, Oriss TB, Huff R, Lee JS, St Croix CM, Watkins S, Mallampalli RK, Kagan VE, Ray A, Ray P. The mito-DAMP cardiolipin blocks IL-10 production causing persistent inflammation during bacterial pneumonia. Nat Commun. 2017 Jan 11;8:3944. doi: 10.1038/ncomms 13944. PMID: 28074841.

Kooijman EE, Swim; LA, Graber ZT, Tyurina YY, Bayir H, Kagan VE.  Magic angle spinning 31P NMR Spectroscopy reveals two essentially identical ionization states for the cardiolipin phosphates in phospholipid liposomes.  Biochim Biophys Acta. 2017 Jan;1859(1):61-68.
doi: 10.1016/j.bbamem 2016.10.013. Epub 2016 Oct 27. PMID: 27984017.

Tyurina, YY, Lou W, Qu F, Tyurin VA, Mohammadyani D, Liu J, Hüttemann M, Frasso MA, Wipf P, Bayir H, Greenberg ML, Kagan VE. Lipidomics Characterization of Biosynthetic and Remodeling Pathways
of Cardiolipins in Geneticlaly and Nutritionally Manipulated Yeast Cells. ACS Chem Bio. 2017 Jan 20:12(1): 265-281. doi:10.1021/acschembio.6b00995. Epub 2016 Dec 16. PMID: 27982579.

Anthonymuthu TS, Kenny EM, Amoscato AA, Lewis J, Kochanek PM, Kagan VE, Bayir H. Global assessment of oxidized free fatty acids in brain reveals an enzymatic predominance to oxidative signaling after trauma.  Biochim Biophys Acta. 2017 Mar 24. pii: S0925-439 (17)30102-3. doi:10.1016/j. bbadis. 2017 [Epub ahead of print] PMID:28347845

Doll S, Proneth B, Tyurina YY, Panzilius E, Kohayashi S, Ingold I, Irmler M,
Beckers J, Aichler M, Walch A, Prokisch H, Trümbach D, Mao G, Qu F, Bayir H, Füllekrug J, Scheel CH, Wurst W, Schick JA, Kagan VE, Angeli JP, Conrad M.  ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2017 Jan;13(1):91-98. Doi:
10.1038/nchembio.2239. Epub 2016 Nov 14. PMID: 27842070.

 Kagan VE, Mao G, Qu F, Angeli JP, Doll S,
Croix CS, Dar HH, Liu B, Tyurin VA, Ritov VB, Kapralov AA, Amoscato AA, Jiang J, Anthonymuthu T, Mohammadyani D, Yang Q, Proneth B, Klein-Seetharaman J, Watkins S, Bahar I, Greenberger, J. Mallampalli RK, Stockwell BR, Tyurina YY, Conrad M, Bayir H. Oxidized arachidonic and adrenic Pes navigate cells to ferroptosis.  Nat Chem Biol. 2017
Jan;13(1):81-90. Doi: 10.1038/nchembio.2238. Epub 2016 Nov 14. PMID: 27842066.

Brand RM, Epperly NW, Stottlemyer JM, Skoda EM, Gao X, Li S, Huq S, Wipf P, Kagan VE, Greenberger JS, Falo LD Jr.  A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage.  J Invest Dermatol. 2017 Mar;137(3):576-586.
Doi: 10.1016/j.jid.2016.09.033.Epub 2016 Oct 26. PMID: 27794421.

 Chiu CF, Dar HH, Kapralov AA, Robinson RAS, Kagan VE, Star A.  Nanoemitters and innate immunity: the role of surfactants and bio-coronas in myeloperoxidase-catalyzed oxidation of pristine single-walled carbon
nanotubes.  Nanoscare. 2017 Apr 25. Doi: 10.1039/c6nr07706d. [Epub ahead of print] PMID: 28440832


Valerian E Kagan
© 2017 by University of Pittsburgh Graduate School of Public Health

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